title: Ghrelin and glucose homeostasis.
abstract: Ghrelin plays an important physiological role in modulating GH secretion, insulin secretion and glucose metabolism. Ghrelin has direct effects on pancreatic islet function. Also, ghrelin is part of a mechanism that integrates the physiological response to fasting. However, pharmacologic studies indicate the important obesogenic/diabetogenic properties of ghrelin. This is very likely of physiological relevance, deriving from a requirement to protect against seasonal periods of food scarcity by building energy reserves, predominantly in the form of fat. Available data indicate the potential of ghrelin blockade as a means to prevent its diabetogenic effects. Several studies indicate a negative correlation between ghrelin levels and the incidence of type 2 diabetes and insulin resistance. However, it is unclear if low ghrelin levels are a risk factor or a compensatory response. Direct antagonism of the receptor does not always have the desired effects, however, since it can cause increased body weight gain. Pharmacological suppression of the ghrelin/des-acyl ghrelin ratio by treatment with des-acyl ghrelin may also be a viable alternative approach which appears to improve insulin sensitivity. A promising recently developed approach appears to be through the blockade of GOAT activity, although the longer term effects of this treatment remain to be investigated.
authors.affiliation: Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands. p.delhanty@erasmusmc.nl
authors.forename: P J D
authors.initials: PJ
authors.lastname: Delhanty
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; C554860:GO-CoA-Tat; D054439:Ghrelin; D007328:Insulin; D010455:Peptides; D054440:Receptors, Ghrelin; D007334:Insulin-Like Growth Factor I; D000217:Acyltransferases; C542776:MBOAT4 protein, human; D005947:Glucose